Wyles Saranya P, Brandt Emma B, Nelson Timothy J
Center for Regenerative Medicine, Mayo Clinic, Rochester, MN 55901, USA.
Int J Mol Sci. 2014 Nov 14;15(11):20948-67. doi: 10.3390/ijms151120948.
Stem cells harbor significant potential for regenerative medicine as well as basic and clinical translational research. Prior to harnessing their reparative nature for degenerative diseases, concerns regarding their genetic integrity and mutation acquisition need to be addressed. Here we review pluripotent and multipotent stem cell response to DNA damage including differences in DNA repair kinetics, specific repair pathways (homologous recombination vs. non-homologous end joining), and apoptotic sensitivity. We also describe DNA damage and repair strategies during reprogramming and discuss potential genotoxic agents that can reduce the inherent risk for teratoma formation and mutation accumulation. Ensuring genomic stability in stem cell lines is required to achieve the quality control standards for safe clinical application.
干细胞在再生医学以及基础和临床转化研究方面具有巨大潜力。在利用其对退行性疾病的修复特性之前,需要解决有关其基因完整性和突变获得的问题。在此,我们综述多能和多能干细胞对DNA损伤的反应,包括DNA修复动力学、特定修复途径(同源重组与非同源末端连接)的差异以及凋亡敏感性。我们还描述了重编程过程中的DNA损伤和修复策略,并讨论了可降低畸胎瘤形成和突变积累固有风险的潜在基因毒性剂。确保干细胞系的基因组稳定性是达到安全临床应用质量控制标准所必需的。